Effect of Acoustic Conditions on Microbubble-Mediated Microvascular Sonothrombolysis

Leeman, Jonathan E.; Kim, Jong Seung; Yu, François T.H.; Chen, Xucai; Kim, Kang; Wang, Jianjun; Chen, Xianghui; Villanueva, Flordeliza S.; Pacella, John J.

doi:10.1016/j.ultrasmedbio.2012.05.020

Cited by 64 publications

(94 citation statements)

References 28 publications

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“…The presence of such oscillating smaller bubbles was already hypothesized by Leeman and co-workers, who found a significant increase in the thrombolytic activity of microbubbles for long ultrasound pulses (> 1000 cycles, 1.5 MPa) over shorter pulses. No increase was observed in case of ultrasound application in the absence of microbubbles [5]. Our preliminary data confirms the presence of stable oscillating bubbles during application of long ultrasound pulses at destructive MI.…”

Section: Discussionsupporting

confidence: 79%

“…In several studies, long ultrasound cycles up to several thousands of cycles were reported to give the best therapeutic effect for microbubblemediated stem cell engraftment [4], thrombolysis [5], gene delivery [6] and reversible opening of the BBB [7]. To understand the therapeutic value of long pulses, an in-depth investigation of the bubble dynamics in response to long pulses is needed.…”

Section: Introductionmentioning

confidence: 99%

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Segmented high speed imaging of vibrating microbubbles during long ultrasound pulses

Kokhuis

Luan

Mastik

et al. 2012

2012 IEEE International Ultrasonics Symposium

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Segmented high speed imaging of vibrating microbubbles during long ultrasound pulses

Kokhuis

Luan

Mastik

et al. 2012

2012 IEEE International Ultrasonics Symposium

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“…In FUS-induced BBB opening, 20,[32][33][34][35][36][37] sonothrombolysis, [38][39][40][41][42] and histotripsy 43,44 studies, correlations between the cavitation activity measured using a single-element passive cavitation detector (PCD) and treatment outcome have been reported. Moreover, microbubble emissions have been used to select treatment pressures 36 and modulate them in real-time between subsequent therapy pulses 35 during FUS-induced BBB opening.…”

Section: Introductionmentioning

confidence: 99%

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Jones

O’Reilly

Hynynen³

2015

Medical Physics

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Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)]. Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections. Conclusions: Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography. C 2015 American Association of Physicists in Medicine.

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“…This critical feature allows us to visualize MB events at various time points of relatively long acoustic tone bursts, which is a crucial capability as the therapeutic efficacy of long pulses for therapeutic applications has become evident. 12,31 In conclusion, our imaging system is capable of both bright field and fluorescent in vitro imaging of MBs at high speed. Its high speed fluorescence imaging capabilities confers the potential for in vivo (fluorescent) high speed observations during intravital microscopy.…”

Section: Conclusion and Discussionmentioning

confidence: 89%

“…10 The ability of US in the presence of MB to accelerate thrombolysis shows the potential for US therapy for myocardial infarction, stroke, and microvascular repair. 11,12 The induction of nonlinear oscillation of MB under US excitation at various conditions is the basis for all contrast enhanced US imaging and therapeutic modalities. The clinical translation of such modalities, particularly US-MB therapeutics, is limited by a poor understanding of the mechanisms by which US-MB interactions exert bioeffects, which in turn is caused by an incomplete understanding of the range of MB acoustic behaviors under the influence of US.…”

Section: Introductionmentioning

confidence: 99%

Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects

Chen

Wang

Versluis

et al. 2013

Review of Scientific Instruments

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High speed imaging has application in a wide area of industry and scientific research. In medical research, high speed imaging has the potential to reveal insight into mechanisms of action of various therapeutic interventions. Examples include ultrasound assisted thrombolysis, drug delivery, and gene therapy. Visual observation of the ultrasound, microbubble, and biological cell interaction may help the understanding of the dynamic behavior of microbubbles and may eventually lead to better design of such delivery systems. We present the development of a high speed bright field and fluorescence imaging system that incorporates external mechanical waves such as ultrasound. Through collaborative design and contract manufacturing, a high speed imaging system has been successfully developed at the University of Pittsburgh Medical Center. We named the system "UPMC Cam," to refer to the integrated imaging system that includes the multi-frame camera and its unique software control, the customized modular microscope, the customized laser delivery system, its auxiliary ultrasound generator, and the combined ultrasound and optical imaging chamber for in vitro and in vivo observations. This system is capable of imaging microscopic bright field and fluorescence movies at 25 × 10 6 frames per second for 128 frames, with a frame size of 920 × 616 pixels. Example images of microbubble under ultrasound are shown to demonstrate the potential application of the system.

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Effect of Acoustic Conditions on Microbubble-Mediated Microvascular Sonothrombolysis

Cited by 64 publications

References 28 publications

Segmented high speed imaging of vibrating microbubbles during long ultrasound pulses

Segmented high speed imaging of vibrating microbubbles during long ultrasound pulses

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects

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